A Randomized Study to Evaluate the Effect of Reminder Notifications and Motivational/Adaptive Messaging on Treatment Adherence (ADVICE)

A 24-week Randomized, Controlled, Multicenter, Open-label Study to Evaluate the Effect of Reminder Notifications and Motivational/Adaptive Messaging on Treatment Adherence of COPD Subjects Receiving Ultibro® Breezhaler® Treatment Using the Concept2 Inhaler for Dose Administration and Tracking

This study was evaluating the effect of reminder notifications and motivational/adaptive messages on treatment adherence behavior in subjects with COPD. The effect will be measured over 24 weeks on the subject's on time treatment adherence and total treatment adherence. The delivery of the medication and tracking of inhaler use is done by the Concept2 inhaler. The reminder notification, feedback on inhaler use and motivational messages are provided by the patient application, who is receiving the inhaler use information from the Concept2 inhaler.

Study Overview

• Status: Terminated
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Combination product: Concept2 inhaler; Combination product: Concept2 inhaler with patient application

Detailed Description

This study was evaluating whether subjects with COPD on Ultibro® Breezhaler® clinical trial formulation once daily dosing regimen using the Concept2 inhaler in conjunction with a patient application collecting data and sending reminder notifications and motivational/adaptive messages aimed at encouraging treatment adherence, have improved treatment adherence compared to subjects using the Concept2 inhaler alone (usual care). The delivery of the medication and tracking of inhaler use is done by the Concept2 inhaler. The reminder notifications, feedback on inhaler use and motivational messages for the subject are sent by the patient application based on the received subjects inhaler use information from the Concept2 inhaler.

The effect will be measured over 24 weeks on the subject's on time treatment adherence (days when the subjects inhaled within +/- 2 hours of the subjects preferred inhalation time) and total treatment adherence (days when patient inhaled at least one dose).

The study population consisted male and female adult patients, 18 years or older with a clinical diagnosis of COPD, a smoking history of 10 pack years, receiving Ultibro Breezhaler treatment for at least 3 months prior to screening and documented poor treatment adherence.

After 6 weeks of screening patients will be randomized to either the Usual Care group in which they will continue to receive Ultibro Breezhaler treatment via the Concept2, or the Telehealth group in which they will additionally receive a tablet device pre-installed with a patient app.

In addition to on time treatment adherence and total treatment adherence, illness and treatment beliefs will be collected via a questionnaire and patient's health status from the EQ5D-5L and SGRQ-C Questionnaire. Key safety assessments are COPD exacerbation and AE/SAE, device deficiencies and device events, drug administration errors, physical exam, vital signs and urine or serum pregnancy test.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 12203
    • Novartis Investigative Site
  • Hamburg, Germany, 20354
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Lubeck, Germany, 23552
    • Novartis Investigative Site
• Netherlands
  • Heerlen, Netherlands, 6419 PC
    • Novartis Investigative Site
  • Helmond, Netherlands, 5707 HA
    • Novartis Investigative Site
  • Leeuwarden, Netherlands, 8934 AD
    • Novartis Investigative Site
  • Zutphen, Netherlands, 7207 AE
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent
• Have a total adherence of more than 10% but less than or equal to 70% during Screening period
• Current or ex-smokers who have a smoking history of at least 10 pack years.
• A diagnosed COPD
• Taking Ultibro® Breezhaler® for at least 3 month prior to Visit 1
• Have been in the Screening period ≥ 35 days.

Exclusion Criteria:

• Pregnant or lactating women
• Women of child-bearing potential
• Subjects having a history of reactions/hypersensitivity to inhaled drugs or drugs of a similar class
• Subjects having a history of reactions/hypersensitivity to lactose or any of the other ingredients of trial medication.
• Subjects with relevant concomitant diseases
• Subjects who have had a COPD exacerbation 6 weeks prior to Visit 1 or between V1 and randomization
• Subjects who have had a respiratory tract infection within 3 weeks prior to Visit 1 or between V1 and randomization
• Use of investigational drugs or other investigational devices at the time of enrollment
• Subjects with a preferred inhalation time between 10.00 pm and 2.00 am.
• Subjects taken off Ultibro® Breezhaler® treatment/inhaler use by the investigator during the Screening period for more than 7 days.
• Subjects not returning all Concept2 inhalers received during the Screening period
• Subjects who have demonstrated inability or unwillingness to use the digital system or to fill in questionnaires.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Usual Care; Concept2 inhaler	Combination product: Concept2 inhaler; Fixed combination of Indacaterol maleate (QAB149) and glycopyrronium bromide (NVA237), 110/50 μg, capsule added to Concept2 inhaler
Experimental: Telehealth; Concept2 inhaler with patient application	Combination product: Concept2 inhaler with patient application; Fixed combination of Indacaterol maleate (QAB149) and glycopyrronium bromide (NVA237), 110/50 μg, capsule added to Concept2 inhaler with application used for monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Participant's On-time Adherence Over 24 Weeks of Intervention Compared to Baseline	On-time treatment adherence was defined as percentage of days on which the participant inhaled at least one dose on-time. Dose inhaled on-time was a dose inhaled within (+ or -) 2 hours of the agreed predefined preferred daily inhalation time (PIT). PIT was defined by the participant at study start.	Baseline 6 weeks, intervention 24 weeks
Change in Participant's Total Adherence Over 24 Weeks of Intervention Compared to Baseline	Total adherence was defined as percentage of days on which the participant inhaled at least one dose and represented the sum of on-time adherence and off-time adherence. Off-time adherence was defined as percentage of days on which the participant did not inhale the daily dose within the (+ or -) 2 hours of the predefined PIT, but outside. The number of doses not inhaled on-time was recorded by the Concept2 inhaler.	Baseline 6 weeks, intervention 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Participant's 6 Weeks Baseline On-time Adherence to the Participant's On-time Adherence Over the Last Four Weeks of Intervention	On-time treatment adherence was defined as percentage of days on which the participant inhaled at least one dose on-time. Dose inhaled on-time was a dose inhaled within (+ or -) 2 hours of the agreed predefined preferred daily inhalation time (PIT). PIT was defined by the participant at study start.	Baseline, Week 21 - 24
Change From Participant's 6 Weeks Baseline Total Adherence to the Participant's Total Adherence Over the Last Four Weeks of Intervention	Total adherence was defined as percentage of days on which the participant inhaled at least one dose and represented the sum of on-time adherence and off-time adherence. Off-time adherence was defined as percentage of days on which the participant did not inhale the daily dose within the (+ or -) 2 hours of the predefined PIT, but outside. The number of doses not inhaled on-time was recorded by the Concept2 inhaler.	Baseline, Week 21 - 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicatrials.com

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2018
• Primary Completion (Actual): January 22, 2019
• Study Completion (Actual): January 22, 2019

Study Registration Dates

• First Submitted: December 15, 2017
• First Submitted That Met QC Criteria: December 15, 2017
• First Posted (Actual): December 20, 2017

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Adherence; Chronic Obstructive Pulmonary Disease; Dose Tracking; Concept2; Digital Adherence System; Ultibro Breezhaler
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: CIDD001D2402

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No